HIV (Human Immunodeficiency Virus (type 1)) belonging to retrovirus is a causative virus of AIDS (Acquired Immunodeficiency Syndrome).
HIV targets CD4 positive cell groups such as helper T cell, macrophage and dendritic cell and destroys these immunocompetent cells to cause immunodeficiency.
Accordingly, a pharmaceutical agent that eradicates HIV in a living organism or suppresses its growth is effective for the treatment or prophylaxis of AIDS.
HIV possesses a bimolecular RNA gene in a shell, which is covered with an envelope protein. The RNA codes for several enzymes (protease, reverse transcriptase, integrase) characteristic of the virus and the like. Translated reverse transcriptase and integrase are present in the shell, and protease is present inside and outside the shell.
HIV contacts and invades a host cell, causes uncoating, and releases a complex of RNA and integrase and the like into the cytoplasm. From the RNA, DNA is transcribed by reverse transcriptase, and a full length double stranded DNA is produced. The DNA moves into the nucleus of the host cell and is incorporated by integrase into the DNA of the host cell. The incorporated DNA is converted to an mRNA by polymerase of the host cell, from which mRNA various proteins necessary for forming a virus are synthesized by HIV protease and the like, and a virus particle is finally formed, which then undergoes budding and its release.
These virus specific enzymes are considered to be essential for the growth of HIV. These enzymes are drawing attention as the target of the development of antiviral agents, and several anti-HIV agents have been already developed.
For example, zidovudine, didanosine, lamivudine, and the like have been already on the market as reverse transcriptase inhibitors, and indinavir, nelfinavir, and the like as protease inhibitors.
In addition, a multiple drug combination therapy concurrently using these pharmaceutical agents has been employed. For example, a combined use of two reverse transcriptase inhibitors (zidovudine and didanosine), and a combined use of three agents of reverse transcriptase inhibitors (zidovudine and lamivudine) and a protease inhibitor (nelfinavir) have been clinically applied. Such multiple drug combination therapy is becoming a mainstream of AIDS therapy (see Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, Aug. 13, 2001).
However, some of these pharmaceutical agents are known to cause side effects such as liver function failure, central nervous disorders (e.g., vertigo), and the like. In addition, acquisition of resistance to a pharmaceutical agent causes a problem. Even worse, emergence of an HIV that shows multiple drug resistance in a multiple drug combination therapy has been known.
Under the circumstances, a further development of a novel pharmaceutical agent, particularly a development of an anti-HIV agent based on a new mechanism, has been desired, wherein a development of an anti-HIV agent having an integrase inhibitory activity is expected, because an integrase characteristic of retrovirus is an essential enzyme for the growth of HIV.
Nevertheless, an effective integrase inhibitor has not been found as yet.
The compounds having an integrase inhibitory activity are described in the following.
WO02/070486 describes the following compounds [A], [B], and the like, as an anti-HIV agent having an integrase inhibitory activity (see WO02/070486 (p. 118, Example I-62, p. 203, Example I-152)).

In addition, WO02/36734 describes the following compound [C] and the like, as an anti-HIV agent having an integrase inhibitory activity (see WO02/36734 (p. 106, Example 3)).

WO02/055079 describes the following compound [D] and the like, as an anti-HIV agent having an integrase inhibitory activity (see WO02/055079 (p. 79, Example 1)).

However, these publications do not include 4-oxoquinoline compound disclosed in the present invention, or a description suggestive thereof.
Now, the compounds comparatively similar to the compound of the present invention are described.
U.S. Pat. No. 3,472,859 describes the following compound [E] and the like, as an anti-bacterial agent or an antimicrobial agent (see U.S. Pat. No. 3,472,859 (column 11, 1. 10)).

In addition, JP-A-48-26772 describes the following compound [F] and the like, as a compound having an antimicrobial activity (see JP-A-48-26772 (p. 6, Example 9); Kyushu Kyoritsu University Research Report, Faculty of Engineering, No. 14, March 1990, pp. 21-32; Memoirs Kyushu Inst. Tech., (Eng.) No. 14, 1984, pp. 13-16).

Furthermore, the following compound [G] and the like are pharmacologically evaluated, as a dehydrogenase inhibitor (see Journal of Medicinal Chemistry, vol. 15, No. 3, pp. 235-237, 1972, Table 1).

In addition, JP-A-2002-534416 (patent family: WO00/40561, U.S. Pat. No. 6,248,739, EP1140850) describes the following compound [H] and the like, as a synthetic intermediate for a compound having an antivirus activity (see JP-A-2002-534416 (p. 141, Formula 60)).

JP-A-2002-534417 (patent family: WO00/40563, U.S. Pat. No. 6,248,736, EP1140851) also describes the following compound [J] and the like, as a synthetic intermediate for a compound having an antivirus activity (see JP-A-2002-534417 (p. 34, Formula 18)).

Moreover, WO01/98275 (patent family: U.S. 2001/103220) also describes the following compound [K] and the like, as a synthetic intermediate for a compound having an antivirus activity (see WO01/98275 (p. 39, 1. 29)).

JP-A-4-360872 (patent family: U.S. Pat. No. 5,985,894, EP498721B1) describes the following compound [L] and the like, as a compound having an antagonistic activity against anti-angiotensin II receptor (see JP-A-4-360872 (p. 64, Table 1)).

WO2004/046115 (patent family: JP-B-3567162) describes the following compounds [M] and the like, as an anti-HIV agent having an integrase inhibitory activity (see WO2004/046115).
wherein ring Cy is an optionally substituted C3-10 hydrocarbon group or an optionally substituted heterocyclic group, R1 is an optionally substituted C3-10 alkyl or the like, R2 is a hydrogen atom or the like, R31 is a hydrogen atom or the like, X is C—R32 or a nitrogen atom, Y is C—R33 or a nitrogen atom (wherein R32 and R33 are independently a hydrogen atom or the like).